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Oncogene ; 30(46): 4656-65, 2011 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-21643019

RESUMO

The ΔNp63 protein, a product of the TP63 gene that lacks the N-terminal domain, has a critical role in the maintenance of self renewal and progenitor capacity in several types of epithelial tissues. ΔNp63 is frequently overexpressed in squamous cell carcinoma (SCC) and in some other epithelial tumours. This overexpression may contribute to tumour progression through dominant-negative effects on the transcriptionally active (TA) isoforms of the p53 family (TAp63, TAp73 and p53), as well as through independent mechanisms. However, the molecular basis of ΔNp63 overexpression is not fully understood. Here, we show that the expression of ΔNp63 is regulated by the Wnt/ß-catenin pathway in human hepatocellular carcinoma (HCC) and SCC cell lines. This regulation operates in particular through TCF/LEF sites present in the P2 promoter of TP63. In addition, we show that ΔNp63 and ß-catenin are frequently coexpressed and accumulated in oesophageal SCC, but not in HCC. These results suggest that activation of the ß-catenin pathway may contribute to overexpression of ΔNp63 during tumour progression, in a cell type-specific manner.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Neoplasias Hepáticas/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , beta Catenina/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Neoplasias Esofágicas/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Regiões Promotoras Genéticas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/metabolismo , beta Catenina/metabolismo
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